N-Acetylcysteine – Amazed at the Research

It is prescribed to you in hospital for paracetamol overdose and if administered in time will save from death by acute liver failure!

More and more research is coming to light about the wonderful benefits of this nutrient.

The main mechanism of action is that it replenishes glutathione (GSH) stores, it may also have an anti inflammatory action, aid in the clearance of mucus and facilitate dopamine release.

Below is a list of recent research across a whole range of body systems including mental health, liver and kidney function, digestive, respiratory, toxicities, sports nutrition, autism, fertility and reproductive, immune, cardiovascular, addictions… I am amazed.

NAC = N-Acetylcysteine GSH = Glutathione

ADDICTIONS

Cannabis Addiction(1)

1200mg twice daily 8 weeks

Randomised double-blind placebo-controlled trial

When drug tested, participants who received NAC had a twofold increase in likelihood of a negative urine cannabinoid test during treatment. NAC was well-tolerated with minimal adverse effects.

Cocaine Addiction(2)

2400mg/day split over 4 doses

3 days Double-blind placebo-controlled trial

The cocaine-dependant participants who received NAC had a reduced overall interest in cocaine (in response to pictorial slides) as well as a reduced desire to use cocaine.

Nicotine Addiction(3)

1200mg/day 6 months

Double-blind placebo-controlled trial.

The participants who received NAC showed decreased markers of DNA damage compared to the placebo group, demonstrating a decrease in oxidative stress.

Nicotine Addiction(4)

1800mg twice daily 3.5 days

Double-blind placebo-controlled trial

The participants who received NAC had fewer withdrawal symptoms and a less rewarding experience with 1st cigarette smoked after trial abstinence.

Nicotine-Dependent Pathological Gambling (5)

1200-3000mg/day 12 weeks Randomised

double-blind placebo-controlled trial

Significant benefit seen in NAC group vs placebo group on Fagerstrom Test for nicotine dependence and measures of problem gambling severity.

Pathological Gambling(6)

1800mg/day 6 weeks Open-label double-blind placebocontrolled randomised trial 16 out of 29 participants who suffered from confirmed pathological addiction to gambling who also received NAC experienced significant reductions in gambling behaviour over the trial period.

BEHAVIOURAL CONCERNS

Nail Biting(7)

1000mg twice daily 24 weeks

Case report A complete abstinence from nail biting and related symptoms was observed amongst all of the patients. NAC’s beneficial effect was observed to continue even after the cessation of treatment.

Skin Picking (8)

1200mg-2400mg/day

12 weeks Double-blind placebo-controlled trial

The participants who received NAC had both a reduced urge to pick, as well as a reduction in the act of skin picking over the treatment period.

Trichotillomania (TTM) Adult (9)

1200mg-2400mg/day

12 weeks Double-blind placebo-controlled trial

The participants who received NAC had a significantly greater reduction in hair-pulling symptoms as measured by MGH-HPS, PIT, and CGI severity scales than those who received placebo.

The participants who received both NAC and the ACE inhibitor had significant reductions in both systolic and diastolic blood pressure.

Non-Insulin Dependent Diabetes(14)

1200mg/day 4 weeks

Randomised cross-over doubleblind clinical trial

The participants who received NAC showed a decrease in plasma vascular cell adhesion molecule (VCAM) and intraerythrocytic GSSG, with an increase in both the GSH concentration overall and in the GSH:GSSG ratio. These results showed promise in slowing the progression of vascular damage.

HEPATIC/RENAL HEALTH

Non-Alcoholic Fatty Liver Disease (NAFLD) (24)

600mg/12 hours 12 weeks

Comparative study

After three months of treatment, participants who received NAC had significantly lower levels of serum alanine aminotransferase. This effect was found to be independent of the grade of steatosis prior to the intervention. NAC was also found to significantly reduce the span of the spleen.

Non-Alcoholic Steatohepatitis (NASH) (25)

1200mg/day + metformin 52 weeks

Comparative study

This study showed that serum alanine aminotransferase, high-density lipoprotein, insulin, glucose concentrations and the homeostatic model assessment (HOMA) index were significantly reduced at the end of study. NAC was also observed to decrease liver steatosis and fibrosis.

Endothelial Dysfunction (ED) – Chronic kidney Disease(26)

600mg twice daily 6 weeks

Controlled clinical trial

Compared to controls, those on haemodialysis were found to have reduced flow-mediated dilatation – a measure of vasodilation. NAC was found to prevent the reduction in flow-mediated dilatation, suggesting that NAC treatment could improve ED.

Cardiorenal Syndrome (27)

500mg twice daily 4 weeks

Double blind crossover placebo-controlled trial

An improvement in endothelial function, and forearm blood flow in the NAC treatment group was observed compared to the placebo group.

Nephropathic Cystinosis (28)

25mg/kg/day 3 months

Controlled clinical trial

Renal function was significantly improved and oxidative stress reduction was seen in the NAC treatment group.

MENTAL HEALTH

ADHD (35) (in patients with SLE)

2400-4800mg/ day 3 months

Randomised double-blind placebo-controlled trial

Clinically significant symptom reduction of ADHD was observed in the NAC treatment group. Reporting completed in accordance to the ADHDself-report scale.

Alzheimer’s Disease(36)

50mg/kg/day 24 weeks

Double-blind placebocontrolled trial

Improved cognitive performance was observed in those who received NAC, with no change in peripheral measures of oxidative stress.

Results showed significant improvements on the Aberrant Behaviour Checklist (ABC) irritability subscale in particular in symptoms such as irritability, stereotypic behaviour, inappropriate speech and lethargy/social withdrawal. The dose was well-tolerated with limited side effects.

The participants who received NAC had a significant improvement in the Montgomery Asberg Depression Rating Scale (MADRS) and Bipolar Depression Rating Scale (BDRS) compared to those who received placebo. The effects were evident after 8 weeks of treatment with NAC.

Depression(40)

1000mg twice daily (adjunctive treatment) 16 weeks

Double-blind randomised placebo-controlled trial

Benefit seen in those with more severe depression in the middle tertile age group. Significant rate of reduction of symptom severity from baselineto endpoint.

Mania(41)

1000mg twice daily 24 weeks

Placebo-controlled randomised trial

Improvement seen in manic symptoms in Young Mania Rating Scale scores while depressive symptoms worsened in the placebo group.

Obsessive Compulsive Disorder(42)

300mg/day 6 weeks

Case report

A reduction in symptoms was seen, with a distinctive improvement seen in behaviour from baseline to endpoint.

Obsessive Compulsive Disorder(43)

600-2400mg daily 12 weeks

Randomised double-blind placebo-controlled trial

Treatment group showed a significantly improved mean Yale-Brown Obsessive Compulsive Scale score. 52% of which were full responders by the study endpoint.

Schizophrenia (44)

1000mg twice daily 24 weeks

Randomised double-blind multi-centre placebo controlled trial

A significant improvement was observed in negative symptoms based on the Positive and Negative Symptoms Scale (PANSS). These improvements were reversed within one month of stopping the NAC.

Traumatic Brain Injury (45)

1500-2000mg twice daily 1 week

Randomised double-blind placebo-controlled study

NAC group showed a complete resolution of their mild traumatic brain injury symptoms, such as headaches, hearing loss and neurocognitive

dysfunction.

IMMUNE

Allergic Rhinitis (29)

50mg-250mg/kg/day

In vitro studies

NAC significantly inhibited the accumulation of inflammatory cells, down-regulated inflammatory molecules such as TNF? and decreased the expression of COX-2. The findings suggest that NAC may be able to suppress the allergen-induced nasal inflammatory cascade.

Helicobacter Pylori Infection (30)

400mg three times daily + Clarithromycin and Lansoprazole 10 days

Controlled clinical trial

NAC was observed to have an additive effect on the eradication rates of H. pylori obtained with dual therapy using Lansoprazole and Clarithromycin. The authors suggest that NAC may have improved the delivery of the antibiotics at the site of infection due to its ability to reduce the thickness of the mucous.

Human Immunodeficiency Virus (HIV) (31)

100mg daily 52 weeks

Randomised placebocontrolled trial

Participants suffering from HIV infection who received NAC had increased levels of sulfur-containing amino acids and GSH, while the control group who received NAC had equalised taurine and GSH levels.

Influenza (32)

600mg twice daily 24 weeks

Controlled randomised and double-blind model

NAC treatment was well tolerated and resulted in a significant decrease in the frequency of influenza-like episodes, severity and length of time confined to bed. Both local and systemic symptoms were significantly reduced in the NAC group – in particular the elderly high-risk group.

Sjögren’s Syndrome (33)

200mg three times daily 4 weeks

Double-blind crossover trial

NAC was observed to improve ocular soreness and irritability, as well as halitosis and daytime thirst.

Systemic Lupus Erythematosus (SLE) (34)

600mg-2400mg twice daily 12 weeks

Double-blind placebo-controlled phase I/II study

NAC increased GSH in peripheral blood lymphocytes and improved disease activity in SLE patients. The authors suggest that NAC may be able to safely improve lupus disease activity by blocking mTOR in T lymphocytes.

Ulcerative Colitis (200)

N-acetyl-L-cysteine combined with mesalamine in the treatment of ulcerative colitis patients with mild to moderate UC were randomized to receive a four-wk course of oral mesalamine (2.4 g/d) plus N-acetyl-L-cysteine (0.8 g/d)

Randomized, placebo-controlled pilot study

Analysis per-protocol criteria showed clinical remission rates of 63% after 4 wk treatment. The clinical improvement correlates with a decrease of chemokines such as MCP-1 and IL-8. NAC addition not produced any side effects.

TOXICITIES

Chemotherapy Adverse Effects (53)

1200mg/day 12 treatment cycles

Randomised controlled trial

NAC was found to reduce the incidence of oxaliplatin-induced neuropathy in colon cancer patients receiving oxaliplatin-based adjuvant chemotherapy.

Heavy Metals(54)

200-400mg once daily or twice daily 12 weeks

Randomised controlled trial Compared to their baseline data, the participants who received NAC had significantly lower serum lead levels. NAC decreased oxidative stress in workers exposed to lead through stimulating GSH synthesis.

SPORTS NUTRITION

Cardiovascular Performance (55)

600mg twice daily 9 days

Double-blind randomised placebo-controlled trial

The treatment group had an improvement in sprint performance during cycling performance via promoting adaptive processes and improvements in redox balance.

NAC decreased mean power output and altered substrate metabolism and muscle fibre type recruitment during the exercise, which is vital to time-trial performance.

Overall Athletic Performance (58)

600mg twice daily 1 week

Randomised placebo controlled trial

Controlled lactate production, maintained total antioxidant capacity, maximised oxygen uptake and improved muscle fatigue was seen in the

treatment group.

RESPIRATORY

Bronchiolitis (46)

1800mg/day 16 weeks

Double-blind model

Dyspnoea, cough, sputum, and wake-up dyspnoea were improved in those who received NAC compared to those who received the placebo. After 4 months, spirometric components were also significantly improved in those who received NAC compared to those who received placebo.

Chronic Bronchitis (47)

200-600mg twice daily 24 weeks

Placebo-controlled double-blind parallel group study

The exacerbation rate was significantly lower in those who received NAC – with 40% of the patients remaining free from exacerbations compared to 19% who received placebo.

Significant improvement in forced expiratory flow, forced oscillation technique, as well as a reduction in exacerbation frequency and small airway function.

Cystic Fibrosis (50)

600mg-1000mg three times daily 4 weeks

Phase 1 study

NAC was seen to offset the inflammatory and redox imbalance commonly seen in Cystic Fibrosis.

Obstructive Sleep Apnoea (51)

600mg three times daily 4 weeks

Randomised placebocontrolled trial

A significant improvement in sleep/respiratory parameters, snore characteristics and beneficial effects on oxygen saturation were observed. Based on these findings, the authors suggest that NAC may also reduce dependency on continuous positive airway pressure therapy.

CHILDREN’S RESPIRATORY

Fever, cough, dyspnoea and thoracic moist rates returned to normal in a significantly shorter time with NAC than with placebo.

Bronchitis (16)

100-200mg three times daily 4 days

Controlled trial

NAC was observed to shorten the duration of catarrhal inflammation of the throat and cough as well as return vital capacity and pulmonary air flow values to normal in patients with either simple or recurrent catarrhal bronchitis after 4 days of treatment.

FERTILITY AND REPRODUCTION

Endometriosis (18)

600mg three times daily for 3 days/ week 12 weeks

Observation cohort study

NAC was found to both prevent the growth of cysts as well as reduce the size of existing cysts. 50% (24 patients) of the NAC treated group cancelled their scheduled laparoscopy due to either decreased or disappeared cysts, pain reduction or pregnancy.

Female Infertility (19)

1200mg NAC + 50mg Clomiphene citrate twice daily 2 months

Prospective cross-over trial

Ovulation rate improved by 52.1% in the NAC group. Endometrial thickness was also significantly improved.

Male Infertility (20)

600mg/day + 200mg selenium 26 weeks

Double-blind placebocontrolled randomised study

The participants who received NAC were observed to have improvements in all semen parameters. A reduction in follicle-stimulating hormone (FSH) and an increase in serum testosterone and inhibin B was also observed, as was an overall improvement in semen quality.

Miscarriage Prevention (21)

600mg/day + 500µg folic acid Up to 20 weeks gestation

Controlled clinical trial

Compared with folic acid alone, NAC + folic acid considerably reduced the rate of a miscarriage up to and beyond 20 weeks.

Polycystic Ovarian Syndrome (PCOS) (22)

1800 or 3000mg/day 5-6 weeks

Randomised placebo- controlled trial

Compared to baseline data, decreases were observed in the hirsutism score, body mass index and HOMA index, and improvements were seen in insulin sensitivity, menstrual irregularity and free testosterone.

Oral NAC was found to reduce the recurrence of preterm birth in patients with bacterial vaginosis. More of the patients in the NAC group reached 36 weeks of pregnancy than in the placebo group. The gestational age at delivery was also significantly higher in the NAC group than in the placebo group.